Signaling pathways play central roles in nearly every tissue context and in many diseases, including cancer, making them major targets for drug development. Rational drug design approaches can successfully target specific pathway components, but still lack necessary cell type or cell context specificity, and therefore can lead to unwanted side effects.
For many of the intercellular signaling pathways such as Bone Morphogenetic Protein (BMP), Wnt, Notch, and JAK-STAT, rather than using a single ligand and receptor, these systems comprise multiple ligand and receptor variants that interact promiscuously with one another to combinatorially generate a large set of distinct signaling complexes. These complexes activate the same intracellular targets, and therefore appear to operate redundantly. The use of redundant ligands and receptors has been thought to offer regulatory flexibility or provide robustness to genetic variation. However, redundancy does not appear to provide a complete understanding of these pathways. Methods to more specifically manipulate signaling pathways are desirable in many applications, including cell-based therapeutics and directed cell differentiation.